Apart from its well known vasodilatory effects, vasoactive intestinal peptide (VIP) has wide ranging and potent releasing actions on many peptide hormones. Among the most interesting are the release of pancreatic insulin and glucagon and pituitary growth hormone, for which we have developed assay methods in the rat. The close sequence homologies, but differing bioactivity spectra of VIP, secretin, glucagon, and gastric inhibitory polypeptide (GIP) suggest that it should be possible to dissociate the biological effects of VIP by the synthesis of analogs. This can now be accomplished routinely due to the development of a rapid solid-phase synthesis of VIP in this laboratory. Such an approach is strengthened by the ease with which selective analogs of somatostatin, another neuro-GI peptide with numerous effects on the release of other peptides, have been recently obtained. VIP analogs with selective activities could have useful therapeutic properties in several disease states, notably some forms of diabetes mellitus. As with other peptides, the development of structure-activity relationships for VIP should help to elucidate its modes of action and also perhaps those of secretin and glucagon.